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502 Background: The phase 3 KATHERINE study (NCT01772472) compared adjuvant T-DM1 versus H in patients with residual invasive breast cancer after neoadjuvant chemotherapy plus HER2-targeted therapy. Here we report exploratory analyses of the relationship between invasive disease-free survival (IDFS) and biomarkers potentially related to response. Methods: Formalin fixed paraffin-embedded tissue samples were collected before neoadjuvant treatment and/or at surgery. Surgical samples were used for analyses, except when only pre-treatment samples were available (~20% of cases). DNA was derived to identify PIK3CA hotspot mutations and gene expression (RNA) analysis was used to detect HER2, PD-L1, CD8 and predefined immune signatures including 3-gene, 5-gene, Teffector, chemokine signaling, and checkpoint inhibitor signatures. RNA analysis was adjusted for tumor content and expression levels were dichotomized at the median into low (≤) and high (>) groups. The effect of treatment and biomarkers on IDFS was assessed. Results: PIK3CA mutation (mut) status was available from 1363 (91.7%) patients. T-DM1 IDFS benefit was independent of PIK3CA mut status (mut: HR 0.54; 95%CI 0.23–0.90; non-mut: HR 0.48; 95%CI 0.35–0.65) and no impact of PIK3CA mut was observed within either treatment arm. Gene expression data were available from 1059 (71.3%) patients. Similar gene expression levels were observed between treatment arms, but, unlike the surgical samples (n = 815), the pre-treatment samples (n = 244) were not representative of the ITT population. Thus, subsequent analyses were based on surgical samples (H n = 398; T-DM1 n = 417). Consistent treatment benefit with T-DM1 vs H was observed across the single-gene and immune gene-signature subgroups as in the ITT population. High vs low HER2 expression was associated with worse outcome (HR 2.02; 95% CI 1.32–3.11) within the H arm, but not within the T-DM1 arm (HR 1.01; 95% CI 0.56–1.83). High vs low PD-L1 expression was associated with better outcome within the H arm (HR 0.66; 95% CI 0.44–1.00) but not within the T-DM1 arm (HR 1.05; 95% CI 0.59–1.87). Similar trends were observed in the checkpoint inhibitor subgroups. Conclusions: These exploratory analyses provide the first data on the relationship between biomarker expression in residual disease after HER2-targeted therapy and outcomes. PIK3CA mut status did not influence outcomes with H or T-DM1. T-DM1 benefit appeared to be independent of all biomarkers assessed. Clinical trial information: NCT01772472 .

BackgroundThe advancements in cancer therapy have improved the clinical outcomes of cancer patients in recent decades. However, advanced cancer therapy is expensive and requires good health care systems. For kidney cancer, no studies have yet established an association between clinical outcome and health care disparities.MethodsWe used the mortality-to-incidence ratio (MIR) for kidney cancer as a marker of clinical outcome to compare World Health Organization (WHO) country rankings and total expenditures on health/gross domestic product (e/GDP) using linear regression analyses.ResultsWe included 57 countries based on data from the GLOBOCAN 2012 database. We found that more highly developed regions have higher crude and age-standardized rates of kidney cancer incidence and mortality, but a lower MIR, when compared to less developed regions. North America has the highest crude rates of incidence, but the lowest MIRs, whereas Africa has the highest MIRs. Furthermore, favorable MIRs are correlated with countries with good WHO rankings and high e/GDP expenditures (p < 0.001 and p = 0.013, respectively).ConclusionsKidney cancer MIRs are positively associated with the ranking of health care systems and health care expenditures.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4698-6) contains supplementary material, which is available to authorized users.

Background: Anxiety and depression continue to be significant comorbidities for people with HIV infection. We investigated the prevalence of and factors associated with anxiety and depression among adult HIV-infected patients across China.Methods: In this cross-sectional study, we described clinical and psychosocial variables related to depression and anxiety in 4103 HIV-infected persons. Doctors assessed anxiety and depression by asking patients whether they had experienced anxiety or depression in the prior month. Patients also self-administered the Hospital Anxiety and Depression (HAD) scale; those with score ≥8 on HAD-A/D were considered to be at high risk of anxiety or depression.Results: Associations between socio-demographic, psychosocial, and ART-related clinical factors and risk of depression or anxiety were investigated using multivariable logistic regression. Among patients assessed between 9/2014 and 11/2015, 27.4% had symptoms of anxiety, 32.9% had symptoms of depression, and 19.0% had both. Recentness of HIV diagnoses (P = 0.046) was associated with elevated odds of anxiety. Older age (P = 0.004), higher educational attainment (P < 0.001), employment (P = 0.001), support from family / friends (P < 0.001), and sleep disturbance (P < 0.001), and number of ART regimen switches (P = 0.046) were associated with risk of depression, while neither sex nor transmission route showed any associations. There were no significant associations with HIV-specific clinical factors including current CD4+ T cell count and current viral load.Conclusions: Prevalence of symptoms of anxiety and depression is high in this cohort of treatment-experienced HIV patients. Psychological and social-demographic factors, rather than HIV disease status, were associated with risk of depression and anxiety. This finding highlights the need to deliver interventions to address the mental health issues affecting HIV-infected persons with fully successful immune restoration across China.

The mortality-to-incidence ratio (MIR) is associated with the clinical outcome of cancer treatment. For several cancers, countries with relatively good health care systems have favorable MIRs. However, the association between lung cancer MIR and health care expenditures or rankings has not been evaluated. We used linear regression to analyze the correlation between lung cancer MIRs and the total expenditures on health/gross domestic product (e/GDP) and the World Health Organization (WHO) rankings. We included 57 countries, for which data of adequate quality were available, and we found high rates of incidence and mortality but low MIRs in more developed regions. Among the continents, North America had the highest rates of incidence and mortality, whereas the highest MIRs were in Africa, Asia, Latin America, and the Caribbean. Globally, favorable MIRs correlated with high e/GDP and good WHO ranking (regression coefficient, −0.014 and 0.001; p = 0.004, and p = 0.014, respectively). In conclusion, the MIR for lung cancer in different countries varies with the expenditure on health care and health system rankings.